PUBLIC VERSION
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`MYLAN PHARMACEUTICALS INC. and AMNEAL
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`PHARMACEUTICALS LLC,
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`Petitioners
`V
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`YEDA RESEARCH AND DEVELOPMENT CO. LTD.
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`Patent Owner
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`Case No. IPR2015—00643 (8,232,250 132)
`Case No. IPR2015—00644 (8,399,483 B2)
`Case No. IPR2015-00830 (8,969,302 B2)“ 2
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`DECLARATION OF PROF. JOEL W. HAY
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`1
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`Case Nos. IPR2015w01976, IPR2015~01980 and IPR2015-01981 have been
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`joined with these proceedings.
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`2
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`A word-for-word identical Deelaration is being filed in each proceeding.
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` JWs
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`g DEPOSITION
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`EXHIBIT
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`MYLAN PHARMS. INC. EXHIBIT 1099 PAGE 1
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`Page 1 of 128
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`Biogen Exhibit 2212
`Mylan v. Biogen
`IPR 2018-01403
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`Page 1 of 128
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`Biogen Exhibit 2212
`Mylan v. Biogen
`IPR 2018-01403
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`TABLE OF CONTENTS
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`I.
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`II.
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`INTRODUCTION. ......................................................................................... 1
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`BACKGROUND AND QUALIFICATIONS ................................................ 2
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`III.
`
`RELEVANT LEGAL CONCEPTS. .............................................................. 8
`
`IV.
`
`SUMMARY OF OPINIONS ........................................................................ 10
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`V.
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`OPINIONS AND THE REASONS AND BASES FOR MY
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`OPINIONS .................................................................................................... 15
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`A.
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`Dr. Grabowski Has Not Defined the Relevant Market ...................... 16
`
`1.
`
`Dr. Grabowski Makes N0 Attempt to Actually
`Define the Relevant Market and Excludes Key
`Drugs from His Analyses ......................................................... 16
`
`B.
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`Dr. Grabowski Fails to Use Accurate and Reliable MS
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`Drug Sales Data, ................................................................................ 19
`
`C.
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`D.
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`Dr. Grabowski Failed to Account for Different Dosing
`Protocols. ............................................................................................ 23
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`Dr. Grabowski Has Not Demonstrated that Copaxone is a
`Commercial Success ........................................................................... 28
`
`I.
`
`2.
`
`3.
`
`Copaxone 40mg/mL Sales Are Fully Accounted
`for by Price Discounting Relative to Copaxone
`20mg/rnL and Glatopa ............................................................. 28
`
`Dr. Grabowski Does Not Address Profitability or
`ROI. .......................................................................................... 33
`
`Financial Analyst Reports Fail to Demonstrate
`Commercial Success of Copaxone 40mg/mL .......................... 35
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`4.
`
`Teva’s Promotion of and Economic Incentives to
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`Switch to Cepaxone 40mg/mL Was an Important
`Driver of Sales. ........................................................................ 37
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`5.
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`No Nexus Shown with Regard to Why Copaxone
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`40mg/rnL Displaced other MS Drugs including
`Copaxone 20mg/mL ................................................................. 42
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`Patient and Physician ATU Surveys Do Not
`Establish Nexus ........................................................................ 43
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`Teva’s Allegediy Limited Marketing and
`Promotion of Copaxone 40mg/mL. ......................................... 44
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`6.
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`7.
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`VI. MISCELLANEOUS. ..................................................................................... 46
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`VII. EXHIBITS AND RESERVED RIGHTS. .................................................... 46
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`I.
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`INTRODUCTION
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`1.
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`1, Professor Joel W. Hay, Ph.D., submit this Declaration on behalf of
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`Mylan Pharmaceuticals Inc. and Amneal Pharmaceuticals LLC (Petitioners) in
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`reply to the November 20, 2015 and November 25, 2015 Declaration of Henry G.
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`Grabowski, PhD.
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`(hereinafter “the Grabowski Declaration”)
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`in the above—
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`captioned case.
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`I also respond to Dr. Grabowski’s testimony in his February 10,
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`2016 deposition (hereinafter “the Grabowski Deposition”).
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`2.
`
`I understand that Dr. Grabowski submitted declarations in IPR2015-
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`00643, lPR2015-00644, and IPR2015—00830 each labelled as Exhibit 2133.
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`I also
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`understand that each of the three Declarations submitted by Dr. Grabowski are
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`substantively identical. Accordingly, I address each Declaration herein.
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`3.
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`A copy of my curriculum vitae is attached hereto as Exhibit A. A
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`listing of legal cases Where I have testified at trial or by deposition since 2012 is
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`attached hereto as Exhibit B. A list of materials relied upon is attached here to as
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`Exhibit C.
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`4.
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`This Declaration discloses my opinions regarding, among other
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`things, certain “secondary considerations” as they pertain to US. Patent Nos.
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`8,232,250 (the “’250 patent”) (IPR2015—00643), 8,399,413 (the “’413 patent”)
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`(IPR2015-00644), and 8,969,302 (the “’302 patent”) (IPR2015—00830).
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`I refer to
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`the pertinent patent below as the “patent at issue.”
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`5.
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`My opinion is that Dr. Grabowski has not established commercial
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`success of the Copaxone 40mg/mL formulation of glatiramer acetate or the patent
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`at issue.
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`It is also my opinion that none of the indicia of commercial success that
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`Dr. Grabowski discusses have any nexus to the claims of the patent at issue.
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`6.
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`I reserve the right to supplement this Opinion as new or additional
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`information becomes available to me.
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`7.
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`I am being compensated for my testimony in the present case at my
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`standard rate of $900.00 per hour, plus any reasonable outwof-pocket expenses. No
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`payments to me are contingent upon the outcome of this or any other hearings or
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`litigation or upon the nature of my opinions.
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`II.
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`BACKGROUND AND QUALIFICATIONS
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`8.
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`In 1974, I received my B.A. in Economics, summa cum laude, from
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`Amherst College.
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`I then went on to receive my MA. in Economics in 1975 and
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`my M.Ph. in Economics in 1976 from Yale University.
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`In 1980, I received my
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`PhD. in Economics from Yale.
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`9.
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`I am a tenured Full Professor and Founding Chair of Pharmaceutical
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`Economics and Policy in the School of Pharmacy, with joint appointments in the
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`Department of Economics and at the Schaeffer Center for Health Policy and
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`Economics at the University of Southern California (USC).
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`I also served for 15
`
`years as the USC Project Coordinator for the Rand Evidence~Based Medicine
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`Practice Centers of Southern California funded by the US. Agency for Healthcare
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`Research and Quality.
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`I am a Health Economics Research Scholar at the UCLA
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`Center for Pediatric Vaccine Research.
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`I am a founding member and founding
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`Executive Board member of the American Society for Health Economics
`
`(ASHEcon) and a founding member and founding Executive Board member of the
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`International Society of Pharmacoeconomics and Outcomes Research (ISPOR).
`
`10.
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`From 1978- to 1980, I was an Assistant Research Professor at USC.
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`Then from 1980 to 1984,
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`I was an Assistant Professor in the Department of
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`Behavioral Sciences and Community Health, and the Department of Economics at
`the University of Connecticut.
`I was also a Senior Policy Analyst with Project
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`Hope from 1983 to 1985. Then from 1985 to 1992, I was a Senior Research
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`Fellow at the Hoover Institution at Stanford University. In 1992, I was recruited to
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`USC to found the Department of Pharmaceutical Economics and Policy.
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`I have
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`been a tenured USC faculty member since then.
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`11.
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`I have authored or coauthored over 500 scientific abstracts, reports,
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`and presentations, including 180+ peer-reviewed scientific articles in the fields of
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`pharmaceutical markets, pharmaceutical economics, health economics, outcomes
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`research, disease management, statistics, econometrics, epidemiology, and health
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`care in journals including: American Journal of Cardiology; American Journal of
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`Health-Systems Pharmacy; American Journal ofManaged Care; American Journal
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`of Public Health; Archives of Neurology; Cancer; CNS Drugs; Haemophilia;
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`Health Care Financing Review; Health Economics; Health Policy; JAMA; Journal
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`of AIDS; Journal of the American Geriatrics Society; Journal of Business &
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`Economic Statistics; Journal of Clinical Gastroenterology; Journal of Health
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`Economics; Journal of Health Politics, Policy and Law; Journal of Human
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`Resources; Journal of Managed Care and Specialnz Pharmacy, Journal of the
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`Royal Statistical Association; Medical Care; Pediatrics; and Value in Health.
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`12.
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`In addition to the hundreds of pharmacoeconomic studies that I have
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`conducted,
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`I have published numerous peer-reviewed scientific articles and
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`abstracts on the cost effectiveness and the economic value of drugs; screening
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`programs; and prevention programs.
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`I recently co-authored a peer-reviewed
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`scientific article on the economic value of newer medications in the treatment of
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`Multiple Sclerosis (MS) and I have given formal presentations on this topic at
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`; 3
`.
`.
`recent selentlfic conferences.
`
`3
`
`Ex. 1100, Xinke Zhang; Joel W. Hay & Xiaoli Niu, Cost Effectiveness of
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`Fingolimod, Teriflunomide, Dimethyl Fumarate and Intramuscular Interferon—£175,
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`in Relapsing-Remitting Multiple Sclerosis; 29 CNS Drugs 71 (2015); Ex. 1101,
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`Xinke Zhang; MS & .loel W. Hay; PhD; Cost-eflectiveness of Fingolimod,
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`Teriflunomide, Dimethyl Fumarate and Intramuscular Interferon Beta-la in
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`Relapsing-remitting Multiple Sclerosis; Poster, Monday Morning, PNDZO, ISPOR
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`13.
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`In April 2015,
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`I was one of three invited outside experts who
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`presented to the Directors and Staff of the Office of Medical Policy (Dr. Jonathan
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`Jarow) and the Center for Drug Evaluation and Research (Dr. Robert Temple) at
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`the U.S. Food and Drug Administration (FDA) on the regulation of economics
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`claims for pharmaceutical products.
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`I also contributed on this topic as an invited
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`speaker to the Academy of Managed Care Pharmacy Partnership Forum, FDAMA
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`£14: Improving the Exchange of Pharrrracoeconornic Data in March 2016.
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`14.
`
`I have served as a consultant to the U.S. Centers for Medicare and
`
`Medicaid Services, U.S. Agency for Healthcare Research and Quality, U.S. Centers
`
`for Disease Control and Prevention, U.S. Public Health Service, U.S. Food and
`
`Drug Administration (FDA), U.S. Environmental Protection Agency, Revenue
`
`Canada, Department of Justice Canada, Government of Hungary, Hong Kong
`
`Centre for Economic Research, Hong Kong Medical Executives Association,
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`World Bank, California AIDS Commission, California Medi—Cal Drug Advisory
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`19th Annual International Conference, May 2014, Montreal, Quebec, Canada; Ex.
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`1102, Xinke Zhang, MS & Joel W. Hay, PhD, Cost-efi’ectiveness of Fingolimod,
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`Teriflunomide, Dimerhyl Fumarare and Intramuscular Interferon Beta-1a in
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`Relapsing—remitting Multiple Sclerosis, American Society for Health Economics
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`5th Biennial Conference, June 2014, Los Angeles, CA.
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`Board, County of San Diego Medically Indigent Adult Program, and County of
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`Sacramento Homeless Program.
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`15.
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`I have also written numerous health-related Op-eds published in
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`papers such as Los Angeles Times, New York Times, Newsday, Sacramento Bee,
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`San Diego Union, San Francisco Chronicle, and Wall Street Journal.
`
`I have been
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`interviewed numerous times on television and radio regarding health—related and
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`drug-related policy issues,
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`including media networks such as American Public
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`Media, Australian Broadcasting Corporation, BBC, PBS, CBS, ABC, NBC, NPR,
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`Fox News, C—SPAN, Al Jazeera and Air America.
`
`16.
`
`I have served as a member of the Expert Advisory Panel on Drug
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`Utilization Review, United States Pharmacopeial Convention; an Executive
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`Committee member for the federally sponsored Southern California Evidence-
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`Based Medicine Practice Center; and a member of the JAM Web Site HIV/AIDS
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`Editorial Review Panel.
`
`I also just completed a third consecutive two—year term as
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`a Study Section member for the Extramural Grants Review Program for the
`
`Agency for Healthcare Research and Quality of the US. Department of Health and
`
`Human Services.
`
`17.
`
`From 2004 to 2010, I was a founding member of the Health Policy
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`Scientific Council of the International Society for Pharmacoeconornics and
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`Outcomes Research (ISPOR). From 2006 to 2010, I was founding Co—Chair of
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`ISPOR’s Drug Cost Task Force.
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`In 2010, this Task Force published siX peer-
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`reviewed guideline papers on pharmaceutical costing methodology in the journal
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`Value in Health, all of which I edited and co-authored.
`
`18.
`
`I served as the Founding Editor—in-Chief of Value in Health, the peer—
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`reviewed scientific journal of ISPOR, from its 1998 inception until 2003.
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`In its
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`first scientific citation impact factor, Value in Health was ranked number one in
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`two categories for the year 2004 by the 181 Journal Citation Reports® (JCR) with
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`an impact factor of 3.657. Value in Health led all other journals listed in both the
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`Health Care Sciences and Services category of the JCR Science Edition and in the
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`Health Policy & Services category of the JCR Social Sciences Edition. These
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`categories include all journals relating to health economics and pharmaceutical
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`economics.
`
`19.
`
`I have provided sworn testimony and expert opinions in numerous
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`legal cases and arbitration hearings on issues
`
`relating to pharmaceuticals,
`
`pharmaceutical markets and prescription medications.
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`In particular,
`
`I have
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`provided expert opinions on the commercial success for pharmaceutical products
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`in numerous legal cases (see, e.g., Exhibit B).
`
`In various separate cases I have
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`testified both for plaintiffs and for defendants in these and other legal matters.
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`III. RELEVANT LEGAL CONCEPTS
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`20.
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`I understand that Patent Owner4 has the burden to show the existence
`
`of secondary considerations of non-obviousness.
`
`21.
`
`I understand that commercial success of a product is a “secondary
`
`consideration” that the PTO and the courts may consider in their determination of
`
`the validity of a patent.
`
`I understand that a showing of commercial success can
`
`provide potential evidence that the invention disclosed in a patent was non—obvious
`
`at the time that the application for the patent was filed.
`
`22.
`
`I have been advised that commercial success is a legal construct that
`
`has been established through case law.
`
`I understand that the courts and the PTO
`
`consider a number of factors in determining whether a product is a “commercial
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`success,” including, but not limited to: (1) sales; (2) profits; (3) total prescriptions;
`
`I understand that Yeda Research & Development Co., Ltd.
`
`is the patent
`
`owner of the patent at issue and that Teva Pharmaceuticals Industries Ltd. is the
`
`exclusive licensee of this patent. Teva Mandatory Notices, IPR2015—00643, Paper
`
`No. 6; IPR2015-00644, Paper No. 6;
`
`IPR2015u00830, Paper No. 5.
`
`I also
`
`understand that Teva Pharmaceuticals USA, Inc. is the holder of the New Drug
`
`Application for Copaxone, a drug for which the patents at issue are listed in the
`
`FDA’s Orange Book and that Teva Neuroscience, Inc. markets and sells Copaxone
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`in the United States. Id.
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`(4) market share in prescriptions and dollar shares; (5) rate and growth in market
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`share; (6) displacement of existing products in the market; and (7) the standing or
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`“rank” of the product in the market.
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`I also understand that sales figures alone are
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`not evidence of commercial success—rather, sales must be considered in light of
`
`the relevant market and the product’s return on investments 1 further understand
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`that courts have found that one cannot merely rely on total sales alone to establish
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`“commercial success.” These factors are consistent with my experience and
`
`understanding in evaluating the success of pharmaceutical products, but are by no
`
`means exhaustive.
`
`23.
`
`I understand further that in order for the commercial success of the
`
`product incorporating the patented technology to be relevant for the purpose of
`
`evaluating non-obviousness,
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`there must be a demonstrable nexus between the
`
`claimed invention and the product’s commercial success.
`
`I understand this to mean
`
`that Patent Owners must Show that any alleged commercial success is driven by
`
`and attributable to a patented feature as opposed to some other characteristic of the
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`product or method of selling.
`
`I fiirther understand that where commercial success
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`If one sold a billion hamburgers at $5 each, but gave each customer a $6
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`rebate coupon, sales would be great, but profits and return on investment would be
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`terrible.
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`can be attributed to characteristics of the invention that were already disclosed in
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`the prior art, nonobviousness is not shown.
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`IV.
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`SUMMARY OF OPINIONS
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`24.
`
`Dr. Grabowski has not defined or adequately measured the relevant
`
`market for Copaxone 40mg/rnL, which is crucial for an analysis of commercial
`
`success. A product’s commercial success can only be evaluated in the context of
`
`its relevant market. Dr. Grabowski has left key MS drugs out of his analysis, such
`
`as Tysabri, Novantrone, H.P. Acthar Gel and Prednisolone. Dr. Grabowski admits
`
`that “the majority of Tysabri prescriptions are not reported to EMS.” EX. 2133 1t 32
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`n. 14; see also Ex. 2113. Underreported data is also a problem for other MS drugs,
`
`such as Lemtrada and other inj ectables, including Copaxone 40mg/mL. The IMS6
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`data that Dr. Grabowski used for his market analysis of MS drugs are known to be
`
`incomplete by billions of dollars and are thus unreliable. Dr. Grabowski relied
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`primarily and extensively on IMS data,7 which do not capture all sales of all MS
`
`IMS Health is a third party company that compiles regular reports on sales
`
`and prescriptions of pharmaceutical products through surveys of pharmacies,
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`physicians and insurance companies.
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`7
`
`I understand the raw IMS data reviewed by Dr. Grabowski was not filed
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`with the Board and is not of record in these proceedings.
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`drugs; many MS injectable drugs are either not captured, or are poorly captured, by
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`IMS.
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`25.
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`Regardless of the market considered, Dr. Grabowski also failed to
`
`establish commercial success of Copaxone 40mg/mL. Dr. Grabowski’s analysis of
`
`market sales and prescriptions is flawed even ignoring the incompleteness of his
`
`relied—upon IMS data.
`
`It is well known that IMS-reported branded drug sales data
`
`are based on published list prices (Wholesale Acquisition Costs (WAC), Average
`
`Wholesale Prices (AWPD and fail to capture price discounts, rebates, coupons and
`
`other (often confidential) price reductions that manufacturers use to generate sales,
`
`and are thus unreliable for calculating revenue sales and market shares. Such
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`confidential rebates and discounts are known to be as large as 61% for well—known
`
`branded medications such as Nexiurn,8 and, based on my experience, may be even
`
`larger for other medications. This is highly relevant as it has been reported that
`
`Teva aggressively converted patients from Copaxone 20mg/mL to Copaxone
`
`8
`
`Ex. 1103, Matthew Her-per, Inside The Secret World of Drug Company
`
`Rebates, Forbes Pharma & Healthcare, at 2—4 (May 10, 2012), available at
`
`http://onforbes/ 1yu08HG.
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`40mg/mL and secured preferred payer co‘verage during the time it was facing loss
`
`of patent protection for Copaxone 20 mg/mL.9
`
`26.
`Dr. Grabowski’s analysis also focuses on raw prescription data, using
`an aggregation of “Total Prescriptions” that ignores MS drug dosing differences.
`
`MS drugs have a variety of dosing protocols, ranging from one injection every
`
`three months to two pills per day, as well as different dosing strengths.
`
`Ignoring
`
`this disparity in prescription data presents a flawed analysis of commercial success.
`
`27. A key determinant of commercial success is whether the alleged
`
`commercial embodiment of the patent at
`
`issue, here Copaxone 40mg/rnL,
`
`generated a reasonable return on investment (ROI). Dr. Grabowski failed to
`
`provide any analysis of Copaxone 40mg/mL’s cumulative profitability and ROI.
`
`He failed to consider the R&D costs of COpaxone 40mg/mL,
`
`including post-
`
`approval studies, any licensing royalties, and marketing and promotion costs,
`
`among other costs.
`
`9
`
`EX. 1104 at 3—5, Thomas Reinke, MS Drug Going Generic Without Making
`
`Waves, MANAGED CARE (June 2015), http://bitly/chdeE (last visited Dec. 31,
`
`2015); see also Ex. 1105, Carly Helfand, Why is Novartis’ Copaxone copy
`
`lagging? It’s all about coverage, analyst explains, Fierce Pharma at 1-2 (Sept. 11,
`
`2015) available at http://bitly/liaSBNM.
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`28.
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`Dr. Grabowski also failed to demonstrate a nexus between the alleged
`
`commercial success for Copaxone 40mg/mL and the claims of the patent at issue.
`
`I
`
`understand that Petitioners’ experts, Dr. Green and Dr. Peroutka, have opined that
`
`the ciaims of the patent at issue are obvious in view of and/or disclosed in the prior
`
`art. Therefore, Dr. Grabowski’s evidence of alleged commercial success is tied not
`
`to the claims of the patent at issue, but rather aspects of the claims disclosed in the
`
`prior art.
`
`29.
`
`But most damaging to any nexus argument
`
`that Dr. Grabowski
`
`appears to make is that Teva launched Copaxone 40mg/mL at a price that was
`
`lower than the price for Copaxone 20mg/mL. While fewer injections present an
`
`obvious benefit to patients, Teva’s sales of Copaxone 40mg/mL were driven by
`
`lower prices and higher discounts, rebates, and favorable co-pay benefits. Offering
`
`COpaxone 40mg/rnL as the lowest cost glatiramer acetate formulation certainly
`
`drives sales, but price discounting has no nexus to the claims of the patent at issue.
`
`Dr. Grabowski did not show that Copaxone 40 mg/mL displaced MS products
`
`other than the more expensive glatiramer acetate alternatives. And the evidence
`
`shows that the oral MS products continued to displace Copaxone after the launch
`
`of Copaxone 40mg/mL. Dr. Grabowski failed to break out the component of
`
`demand for Cepaxone 40mg/mL that relates to the fact that
`
`it was the only
`
`Copaxone product that Teva was heavily promoting, marketing and providing
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`generous rebates on, as opposed to the component of demand that relates to its
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`thrice~weekly closing.
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`30.
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`Dr. Grabowski did not consider other possible causes of Copaxone
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`40mg/rnL’s sales other than its thrice-weekly administration. Certainly a large
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`component of Copaxone 40mg/mL’s sales are driven by the fact that many patients
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`wanted to take glatirarner acetate, the active ingredient in both Copaxone 20mg/mL
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`and 40mg/mL.
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`Indeed, the first item listed on Teva’s advertising for Copaxone
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`40mg/mL is the history of safety and efficacy of glatiramer acetate.10 In fact, as
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`Dr. Grabowski’s Exhibits show, COpaxone 40mg/mL — the less expensive
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`product — largely cannibalized existing sales of Copaxone 20mg/mL. See, eg, Ex.
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`2112. Sales of COpaxone 40mg/mL due to patients and physicians comfort level
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`and experience with glatiramer acetate have no nexus to the claims of the patent at
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`issue.
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`31.
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`Furthermore, Dr. Grabowski did not consider whether Copaxone
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`40mg/mL’s sales are' due to relative price changes for other MS drugs, formulary
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`changes, safety warnings or dispensing restrictions on Lemtrada, Tysabri or other
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`MS drugs that had nothing to do with Copaxone 40mg/rnL’s characteristics. Dr.
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`Grabowski cites items in the Copaxone 40mg/mL marketing campaign that he
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`10
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`_ Ex.
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`1106,
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`3-TimeS-A-Week
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`C0pax0ne®
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`40
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`MG,
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`TEVA,
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`https://www.c09axone.com/about-copaxone/copaxone—40-mg.
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`alleges to be relevant to the patent at issue (without explicitly showing nexus)
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`while completely failing to consider a large variety of other factors in the MS
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`pharmaceutical market that are far more relevant to Copaxone 40mg/mL’s raw
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`sales figures than Dr. Grabowski’s incomplete and unreliable IMS Health sales and
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`market share analysis.
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`V.
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`OPINIONS AND THE REASONS AND BASES FOR MY OPINIONS
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`32.
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`In my opinion, Dr. Grabowski has not demonstrated commercial
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`success. Moreover, his alleged indicia of commercial success have no nexus to the
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`claims of the patent at issue.
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`33.
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`As detailed below, Dr. Grabowski’s analysis falls short because he
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`failed to consider which products are in the relevant market (see infia at 111] 34—3 8),
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`omitted important MS drugs from his analysis (see infm at 111] 3438), failed to
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`consider the aggressive price discounting strategy for COpaxone 40mg/mL (see
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`infia at W 53—59, 6972), misinterpreted the limited IMS data provided to him by
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`Patent Owner (see infra at W 39-43), and ignored differences in dosing protocols
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`and usages for different MS drugs ((see infia at 1111 44-51). Dr. Grabowski also
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`failed to consider the R&D costs for Copaxone 40mg/rnL (see infia at W 27, 62),
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`failed to address Teva’s ROI for Cepaxone 401ng/mL (see infra at 1111 60-62), failed
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`to reliably consider MS drug promotional spending (see infia at 1111 66-32), and
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`failed to show that other crucial factors lacking any nexus to the patent at issue
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`were not key to sales of Copaxone 40mg/mL, such as price discounts, price
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`rebates, patient coupons and payment assistance programs, FDA approval,
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`formulary changes for other MS drugs, MS drug safety concerns, the properties of
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`glatiramer acetate, or other market characteristics and/or characteristics of the
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`Cepaxone 40mg/mL product or method of selling that have no nexus to the patent
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`at issue (see infla at W 73-79).
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`A.
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`DR. GRABOWSK] HAS NOT DEFINED THE RELEVANT MARKET
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`I.
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`Dr. Grabowski Makes No Attempt to Actually Define the
`Relevant Market and Excludes Key Drugs
`from His
`Analyses.
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`34.
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`Sales figures alone are not evidence of commercial success—rather,
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`sales must be considered in light of the relevant market. Dr. Grabowski’s opinion
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`is flawed because he sets forth no specific market definition, and neither lists nor
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`fully includes all of the likely competitors within that defined market. Further, Dr.
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`Grabowski admits that he simply accepted the limited IMS data that he was
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`provided by counsel. Ex. 2148 (Grabowski Dep.) at 35:20—36:6, 48:4m8, 51—7—24.
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`Thus, it is my opinion that Dr. Grabowski’s opinion is based on a highly flawed
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`measure of saies for an incomplete list of MS drugs provided by IMS.
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`35.
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`Dr. Grabowski’s anaiysis of monthly “Multiple Sclerosis Drugs: Share
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`of Total Prescriptions” does not include key MS drugs such as Tysabri. See Ex.
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`2113. Tysabri generates more than $1 billion in sales annually.11 Leaving out such
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`a key drug biases the context of Dr. Grabowski’s analysis. Because of the
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`incompleteness of the analyzed data, Dr. Grabowski’s sales and prescription
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`figures have no proper context in which to evaluate commercial success.
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`36.
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`Dr. Grabowski suggests that Copaxone 40mg/rnL competes against all
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`MS drugs, yet he failed to provide any sales data on Ampyra,12 Tysabri,
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`Lemtrada,13 Novantrone, Prednisolone, or HP Acthar Gel and any relevant
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`11
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`According to Biogen, “TYSABRI® revenues were $1.9 billion compared to
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`$2.0 billion in 2014. These results consisted of $1.1 billion in U.S. sales and $7 83
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`million in sales outside the U.S. compared to $1.0 billion and $934 million,
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`respectively,
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`in 2014.” Ex. 1107 at 1, Press Release, Biogen, Biogen 2015
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`Revenues
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`Increase 11% to $10.8 Billion (Jan. 27, 2016),
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`available at
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`htmj/bitly/IOXIHX.
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`12
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`Ampyra is indicated on its label for improving walking in MS patients. Ex.
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`1139 at 1, Ampyra Prescribing Information. Dr. Grabowski failed to justify his
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`exclusion of this and other MS drugs from his market definition.
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`13
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`Alemtuzumab (Lemtrada) was approved for RRMS in November 2014, but
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`Lemtrada is the same as alemtuzumab (Campath), which was available prior to
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`November 2014 in the U.S. as a cancer drug, and was used off~1abel for RRMS
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`prior to that point. See, e.g., Ex. 1108, Multiple Sclerosis Trust, A to Z of MS
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`generics or alternative brands for these products, products with billions of dollars
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`of combined sales. Ex. 2133 (Grabowski Decl.) W 20-32. Other times, Dr.
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`Grabowski suggests that the relevant market is comprised solely of Copaxone
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`40mg/mL and the other two glatiramer acetate drugs: Copaxone 20mg/mL and
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`GlatOpa. See, e.g., Ex. 2121 (showing “net prescriptions flow” for only Copaxone
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`40mg/mL, Copaxone 20mg/mL and Glatopa); Ex. 2133 (Grabowski Decl.)
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`W 33-39.
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`37. Without any meaningful explanation, Dr. Grabowski writes in his
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`Declaration that “Tysabri® is subject to a restricted distribution program so the
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`majority of Tysabri® prescriptions and are not reported to IMS.”14 That IMS does
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`Alemtuzumab (Lemtrada), http://bitJy/lYnIfHQ (accessed June 2, 2015); Ex.
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`1109, Randy Osborne, Buzz Around Campath Proof—ofConcept trial in MS, 27(1)
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`NATURE BIOTECHNOLOGY 6 (2009); Ex. 1110,
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`Jeffrey A. Cohen, et al.,
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`Alemtuzumab versus interferon beta 1a as first-line treatment for patients with
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`relapsing-remitting multiple sclerosis: a randomized controlled phase 3 trial, 380
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`LANCET 1819 (2012).
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`‘4
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`Ex. 2133 1] 32 n.14. One reason that IMS does not capture Tysabri is that for
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`safety reasons it is distributed through a specialty pharmacy to manage its FDA-
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`mandated Risk Evaluation and Mitigation Strategies (REMS) program.
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`IMS does
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`an incomplete job of capturing drugs distributed through specialty pharmacies.
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`not capture (or incompletely captures) sales data for Tysabri and other MS drugs is
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`no reason for Dr. Grabowski to draw faulty market inferences from IMS data on
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`which he chose to focus.
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`38.
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`Because he failed to define the market, omitted entirely important
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`products, and relied on data known to be incomplete, Dr. Grabowski’s analysis is
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`invalid: it excludes Tysabri, which he admits is a direct competitor of Copaxone 40
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`mg/mL with annual US. sales in 2015 of $1 billion, and the IMS data understates
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`sales of many other MS drugs, particularly injectables. No meaningful conclusions
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`can be drawn from an analysis of such incomplete data.
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`B.
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`DR. GRABOWSKI FAILS TO USE ACCURATE AND RELIABLE MS DRUG
`SALES DATA.
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`39.
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`As noted above, Dr. Grabowski
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`failed to provide sales data on
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`Tysabri, Novantrone, Lerntrada, Prednisolone, H.P. Acthar Gel, or generic and
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`alternative brand versions of any of these drugs, all likely competitors to Copaxone
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`Because Lemtrada also requires a REMS program, it is also likely missing from
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`the IMS data for this reason. Novantrone, generic mitoxantrone, H.P. Acthar Gel,
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`- Prednisolone and other MS drugs are likely listed in other IMS therapeutic
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`categories because they have other treatment
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`indications besides MS and/or
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`specialty pharmacy distribution. Again, however, Dr. Grabowski did not provide
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`an explanation for his exclusion of these drugs from his relevant market analysis.
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`40mg/mL. This problem is further compounded by the fact that many of the MS
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`drugs that he considers are injectables,
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`increasingly distributed by specialty
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`pharmacies and/or dispensed in physician offices.
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`Such sales are often not
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`captured in IMS audits.
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`I am aware of this fact because IMS employees
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`themselves have told me about this data problem in detail. Moreover, IMS admits
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`this problem in its own drug utilization reports where it states tha